Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk

• ClinicalTrials.gov Identifier: NCT02272946
• Recruitment Status: Active, not recruiting
• First Posted: October 23, 2014
• Last Update Posted: November 10, 2021
• Sponsor: Priscilla Hsue, MD
• Information provided by (Responsible Party): Priscilla Hsue, MD, University of California, San Francisco

Tracking Information

• First Submitted Date: October 13, 2014
• First Posted Date: October 23, 2014
• Last Update Posted Date: November 10, 2021
• Study Start Date: September 2015
• Actual Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 21, 2014)

• Number of Adverse Events at week 1 as a measure of safety [ Time Frame: Week 1 ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
• Number of Adverse Events at week 2 as a measure of safety [ Time Frame: Week 2 ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
• Number of Adverse Events at week 4 as a measure of safety [ Time Frame: Week 4 ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA
• Number of Adverse Events at week 8 as a measure of safety [ Time Frame: Week 8 ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA
• Number of Adverse Events at week 12 as a measure of safety [ Time Frame: Week 12 ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose, CD4 count, HIV-1 RNA
• Number of Adverse Events at week 18 as a measure of safety [ Time Frame: Week 18 ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose
• Number of Adverse Events at baseline as a measure of safety [ Time Frame: Baseline ]
  Toxicities will be assessed and adverse events will be recorded at the study visit, including abnormal lab values for the following list of labs: CBC, AST, ALT, bilirubin, creatinine, glucose

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 21, 2014)

• Change in brachial artery flow-mediated vasodilation (FMD) [ Time Frame: Baseline, 12 weeks ]
  Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter
• Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT as a measure of vascular inflammation [ Time Frame: Baseline, 12 weeks ]
  Assessed by FDG-PET/CT scanning
• Rate of change in inflammatory markers of CVD risk [ Time Frame: Baseline, 4 weeks, 12 weeks, 18 weeks ]
  Linear mixed modelling will be used to estimate rates of change over the 18 weeks of treatment. Inflammatory markers: high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
• Official Title: Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
• Brief Summary: The purpose of this study is to evaluate the effects of IL-1β inhibition on safety, measures of systemic and vascular inflammation and endothelial function (all indicators of cardiovascular risk) in treated and suppressed HIV infected individuals This study will assess the safety and effects of canakinumab on endothelial function (assessed by flow-mediated vasodilation [FMD] of the brachial artery), vascular inflammation (assessed by FDG-PET/CT scanning), key inflammatory markers of cardiovascular disease (CVD) risk (high-sensitivity C-reactive protein [hsCRP]), interleukin-6 (IL-6), soluble CD163 (sCD163), D-dimer, T-cell and monocyte activation in the blood, and size of the HIV reservoir. 20 individuals will receive a single dose of 150mg canakinumab with follow-up for 18 weeks.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment

Condition

• HIV
• Cardiovascular Disease

Intervention

• Drug: Canakinumab
  150mg Canakinumab received subcutaneously
  Other Name: IL--1β
• Drug: Placebo
  150mg Placebo received subcutaneously

Study Arms

• Safety Arm
  In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
  Intervention: Drug: Canakinumab
• Experimental: Canakinumab
  In Stage II: About 67 subjects will receive 150mg Canakinumab subcutaneous injection.
  Intervention: Drug: Canakinumab
• Placebo Comparator: Placebo
  In Stage II: About 33 subjects will receive 150mg placebo subcutaneous injection
  Intervention: Drug: Placebo

• Publications *: Kentoffio K, Temu TM, Shakil SS, Zanni MV, Longenecker CT. Cardiovascular disease risk in women living with HIV. Curr Opin HIV AIDS. 2022 Sep 1;17(5):270-278. doi: 10.1097/COH.0000000000000756. Epub 2022 Jul 5.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Estimated Enrollment (submitted: May 26, 2015): 110
• Original Estimated Enrollment (submitted: October 21, 2014): 20
• Estimated Study Completion Date: December 2022
• Actual Primary Completion Date: February 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. HIV infection,
2. Age ≥ 40 years < 60 years
3. On continuous ART for at least 12 months with no change in regimen in 12 weeks prior to study entry
4. CD4+ T cell count ≥ 400 cells/mm3
5. HIV RNA level below the standard limit of quantification for 52 weeks prior to entry
6. High risk for CAD as defined by either documented CVD (including prior MI) or diabetes mellitus or 1 CVD risk factor (current smoking, hypertension, dyslipidemia, or hsCRP≥2mg/L.)
7. Individuals on stable doses of lipid lowering therapy and/or anti-hypertensive medication will be allowed in the study.
8. Appropriate documentation from medical records of prior receipt of pneumococcal vaccinations

Exclusion Criteria:

1. Women of childbearing potential or pregnant/nursing women
2. CABG surgery in the past 3 years
3. Class IV heart failure
4. Uncontrolled HTN
5. History of tuberculosis or latent TB that is not treated
6. Nephrotic syndrome or eGFR< 30 ml/min/1.73m2
7. Active hepatic disease or active/chronic hepatitis B or C
8. Any prior malignancy including KS
9. Serious illness requiring hospitalization or active infection requiring antibiotics within 90 days
10. Requirement for live active vaccination 3 months prior to, during, and 3 months after study
11. Concurrent immune modulating therapy
12. Diabetes Mellitus
13. History of multiple imaging studies associated with radiation exposure
14. Neutropenia defined as ANC<1500/mm
15. Triglycerides>400 mg/dL
16. History of hypersensitivity to study drug
17. History of EBV-related lymphoproliferative disorders
18. Active or untreated latent TB infection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 59 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02272946
• Other Study ID Numbers: Canakinumab
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Priscilla Hsue, MD, University of California, San Francisco
• Original Responsible Party: University of California, San Francisco
• Current Study Sponsor: Priscilla Hsue, MD
• Original Study Sponsor: University of California, San Francisco
• Collaborators: Not Provided

Investigators

• Principal Investigator: Priscilla Hsue, MD; University of California, San Francisco

• PRS Account: University of California, San Francisco
• Verification Date: November 2021